This ongoing project evaluates a wide variety of factors which contribute to the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), the norepinephrine metabolite thought best to reflect brain turnover. New findings or replications of earlier ones are as follows: (1) in bipolar patients, 24-hr urinary excretion is low in depression and high in mania but does not predict mood changes; (2) the altered circadian rhythm of MHPG in depressed patients is the basis for a collection of 11 p.m.-7 a.m. urines which may prove especially helpful in current outpatient or normal volunteer research; (3) MHPG changes induced by physical activity can be shown in "well-state" outpatients with a history of manic-depressive episodes; (4) there is a modest positive (0.58) correlation between MHPG of depressed patients and nurses' ratings of their anxiety; (5) there is no correlation between urinary MHPG and urinary free cortisol which is presumably under serotonergic control; (6) systematic comparisons of quantitative methodology indicate that gas chromatography is a reliable means of measuring MHPG and that comparison with GC-MS provides a systematic factor of 0.83 to arrive at a correct absolute value.